Stroke has become the second reason of death and the third reason of disability in the world, of which ischemic stroke accounts for more than 80% of cases. Nerve injury represents the primary reason of high mortality and disability as well as poor prognosis of ischemic stroke, and its mechanisms involve ferroptosis, reactive oxygen species (ROS) burst, inflammation, and so on. However, blood brain barrier (BBB) and "no reflow" phenomenon prevent neuroprotective drugs from reaching the deep region of cerebral ischemia and hypoxia, posing a significant challenge to the neuroprotective treatment.
The teams led by Professor Xianyi Sha from School of Pharmacy of Fudan University, Professor Jing Zhao from Minhang Hospital, and researcher He Wang from Institute of Science and Technology for Brain-Inspired Intelligence of Fudan University jointly designed a biomimetic nanomotor Pt@LF. It facilitates deep delivery of neuroprotective agents in brain and inhibits ferroptosis of neurons in ischemic stroke, providing a new strategy for the neuroprotective treatment of ischemic stroke. Pt@LF traverses BBB and penetrates into deep cerebral ischemic-hypoxic areas due to the active targeting capacity of apo-lactoferrin (Apo-LF) and the self-propelling motion properties of nanomotors. Subsequently, Pt@LF exhibitsvarious antioxidant enzyme-like abilities, iron ion chelating ability and NH4+ scavenging activity,inhibits ferroptosis of neurons with multiple targets, rescues dying neurons and ameliorates the inflammatory microenvironment. In the meantime, Pt@LF loosens thrombus and alleviates the “no reflow” phenomenon via mechanical thrombolysis. Pt@LF reduced the infarct area of tMCAO rats from 27.83% to 4.69% in vivo, and effectively improved the neurological function after ischemic stroke, providing an innovative treatment for neuroprotection of ischemic stroke.
This research was published online in the authoritative journal Advanced Materials under the title of "Biomimetic Nanomotors for Deep Ischemia Penetration and Ferroptosis Inhibition in Neuroprotective Therapy of Ischemic Stroke".
The Biomimetic Nanomotors in Neuroprotective Therapy of Ischemic Stroke
Professor Xianyi Sha from School of Pharmacy of Fudan University, Professor Jing Zhao from Minhang Hospital, and researcher He Wang from Institute of Science and Technology for Brain-Inspired Intelligence of Fudan University are the co-corresponding authors of this paper. Rui Wang, the 2019 Ph.D. from School of Pharmacy of Fudan University, is the first author of this paper. This research was funded by the National Natural Science Foundation of China and the National Key Research and Development Program of the Ministry of Science and Technology.
